title: Oligomerization interface of RAGE receptor revealed by MS-monitored hydrogen deuterium exchange.
abstract: Activation of the receptor for advanced glycation end products (RAGE) leads to a chronic proinflammatory signal, affecting patients with a variety of diseases. Potentially beneficial modification of RAGE activity requires understanding the signal transduction mechanism at the molecular level. The ligand binding domain is structurally uncoupled from the cytoplasmic domain, suggesting receptor oligomerization is a requirement for receptor activation. In this study, we used hydrogen-deuterium exchange and mass spectrometry to map structural differences between the monomeric and oligomeric forms of RAGE. Our results indicated the presence of a region shielded from exchange in the oligomeric form of RAGE and led to the identification of a new oligomerization interface localized at the linker region between domains C1 and C2. Based on this finding, a model of a RAGE dimer and higher oligomeric state was constructed.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sitkiewicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Tarnowski
authors.forename: Jarosław
authors.initials: J
authors.lastname: Poznański
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kulma
authors.forename: Michal
authors.initials: M
authors.lastname: Dadlez
mesh_terms: D003903:Deuterium / Q000737:chemistry*; D005110:Extracellular Space; D006859:Hydrogen / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D013058:Mass Spectrometry; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D055550:Protein Stability; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D006859:Hydrogen; D003903:Deuterium